title: Autoreactive thymic B cells are efficient antigen-presenting cells of cognate self-antigens for T cell negative selection.
abstract: The thymus contains a population of B cells that colocalize with dendritic cells and medullary thymic epithelial cells in the thymic medulla. The development and functional significance of these cells are largely unknown. Using recombination-activating gene 2 GFP reporter mice along with parabiosis experiments, we demonstrate that the vast majority of thymic B cells develop from progenitors within the thymus. Thymic B cells express unique phenotypic markers compared with peripheral B cells; particularly they express high levels of MHC class II, suggesting that they are poised to present self-antigens efficiently. Using Ig knock-in and T-cell receptor transgenic mice specific for the self-antigen glucose-6-phosphate isomerase, we show that autoreactive thymic B cells serve as efficient antigen-presenting cells for T cell negative selection even when they are present at low frequencies. Furthermore, the endogenous thymic B-cell repertoire also functions in this capacity. These results suggest that developing thymic B cells could efficiently capture a broad array of autoantigens through their B-cell receptors, presenting peptides derived from those autoantigens to developing thymocytes and eliminating cognate T cells.
authors.affiliation: Committee on Immunology, Department of Medicine, Section of Rheumatology, and Knapp Center for Lupus and Immunology Research, Department of Pathology, and Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637.
authors.forename: Jason
authors.initials: J
authors.lastname: Perera
authors.forename: Liping
authors.initials: L
authors.lastname: Meng
authors.forename: Fanyong
authors.initials: F
authors.lastname: Meng
authors.forename: Haochu
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D055879:Gene Knock-In Techniques; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell; D005956:Glucose-6-Phosphate Isomerase